Introduction: Milk thistle has been used for centuries as a herbal medicine for the treatment of different diseases. The aim of this study was to investigate the effects of different doses of short-term milk thistle extract supplementation on the inflammatory markers response in active male induced by one-session aerobic exercise.Methods: For this purpose, Twenty-seven active male with VO2max 45-50 ml.kg-1.min, after completing consent forms, in a quasi-experimental and double-blind design were divided in three homogeneous groups of 9 subjects; supplement (Silymarin: 5 and 10 mg.kg1.day) and placebo (Dextrose: 5 mg.kg-1.day). After 14-day supplementation, all subjects were participated in a single aerobic exercise include; running on the treadmill at the 0% slope for 30 min with the intensity of 70-75% HR reserve. Blood samples were taken at three phases (baseline, after supplementation period and 24 hour after the exercise). Data were analyzed using repeated-measure 3×3 ANOVA, Bonferroni and independent t-test at α≤0.05.Results: The results showed that a single bout of aerobic exercise causes a significantly increased 24-hour inflammatory indices in all groups (P=0.001). However, in comparison to the placebo group, silymarin ingestion groups cause to attenuate the inflammatory markers response (CRP & PBMC) for placebo, 5 and 10 mg.kg-1.day of silymarin, respectively; P=0.023 and P=0.014) following one-session aerobic exercise.Conclusion: Based on the present findings, it can be concluded that the short-term of silymarin supplementation in dose-dependent response together with aerobic exercise could reduce the inflammatory markers in active males.